Personalized 3D printing titanium alloy cranial prosthesis can be designed and manufactured based on the patient’s CT data to perfectly match and effectively repair the cranial defect. However, previous studies paid little attention to the impact resistance of the cranial prosthesis. In this paper, a novel personalized 3D printing cranial prosthesis is developed based on the electron beam melting technology. The impact resistance of 3D printing titanium alloy personalized cranial prosthesis and digital 3D forming titanium mesh are measured via the falling ball impact device. Results show that the average maximum deformation of 3D printing titanium alloy personalized cranial prosthesis is 0.7 mm, which is much less than the 5.9 mm average maximum deformation of digital forming titanium mesh. In summary, 3D printing personalized cranial prosthesis has good impact resistance in repairing the cranial defect and protecting the intracranial brain tissue.